The Effects Of Noise-induced Hearing Loss In Postnatal Mice On Cognitive Function And Hippocampal Neurogenesis

Background and goal:Cognitive Impairment(CI)is a serious problem challenging public health worldwide.Several epidemiological surveys have proposed that hearing loss(HL)is an independent risk factor for the development of Cl in the elderly.In addition,school-aged children with HL show lower intelligence level than the age-matched control with normal hearing.With the development of the industrialized society,noise pollution is an increasing environmental problem and a direct or indirect threat to individual’s auditory function and cognitive function.Noise-induced hearing loss(NIHL)has become one of the main forms of acquired hearing loss.In recent years,the prevalence of HL in children and adolescents has increased,largely due to the recreational noise.The impact of noise on cognitive function has long been reported.However,this effect of noise has been largely attributed to the noise-induced oxidative stress and consequent damage to the cognitive function-related brain regions,while the potential effect of HL is largely ignored.In our previous study,an adult animal model with NIHL was established by a single,strong noise exposure that lasted for a short period of time.The long-term effect of stress response was avoided due to the transient feature of the noise exposure.Our results showed that long after the establishment of NIHL,animals exhibited impaired spatial learning and memory,along with a decline in neurogenesis of hippocampal dentate gyrus(DG),which was not changed shortly after the NIHL was established.These results suggest that noise can lead to cognitive impairment by HL,independent of its stress effect.Our previous work also examined the delayed effect of a similar NIHL established at postnatal day 14(P14d)on the cognitive function of C57BL/6J mice.In order to fully understand the effect of the NIHL established in the postnatal development,we duplicated the evaluation of the long-term changes of cognitive function and hippocampal neurogenesis associated with the NIHL established at P21d,and compared the differences with the results of adult animals.Methods:Healthy male C57BL/6J mice were recruited at P20d and used as experimental objects.Before being applied to the experimental procedure,all animals were screened by open field test to exclude the animals that showed low movement ability and abnormal level of anxiety.Then the animals were randomly divided into the control group and the noise exposed groups that were exposed to a broad band white noise at 123 dB SPL for 2 hours(2h)at P21 d.The noise exposed animals were further randomly divided into 1 month post noise(1MPN)group and 3 months post noise(3MPN)group,and the control group divided into the age-matched subgroups for each noise group.Auditory brainstem response(ABR)was used to evaluate the auditory threshold of animals before cognitive function test.Spatial learning and memory function was evaluated with Morris water maze(MWM)test.5-Bromo-2-deoxyUridine(BrdU)injection was given one week before the MWM test.After behavioral test,the animals were perfused and brain tissue were used to examine neurogenesis in DG of hippocampus.In order to analyze the effects of NIHL established at juvenile on hippocampal neurogenesis,the number of cells stained with endogenous markers Ki67 was evaluated as the index of the proliferation rate in hippocampus,and the number of cells stained with exogenous marker BrdU was evaluated as the cells survived from that generated shortly after the BrdU injection.The rescue effect was first determined within the noise and the control group by comparing the survival differences between trained and no-trained subgroups.The impact of NIHL on the rescue effect was further evaluated by the comparison on the rescue effect between the groups.Results:The ABR results showed significantly higher hearing thresholds of NIHL animals in the 1MPN group and 3MPN group as compared to age-matched controls;the averaged thresholds over 4k-16k were 54.78 dB SPL and 60.28 dB SPL higher than that of the control values at the two time points(suggesting a moderate to severe hearing loss).The results of MWM showed that the spatial learning ability of NIHL animals was significantly lower than that of the control group at 1MPN,and learning performance showed significantly positive correlation with the degree of hearing loss.Whereas in 3MPN group,there was no significant difference in the spatial learning ability between NIHL animals and age-matched control animals.However,the correlation analysis indicated that there was a positive correlation between hearing loss and the MWM performance.The NIHL animals did not show a significant difference in spatial memory capacity either at 1MPN or at 3MPN when compared with the age-matched control groups.The results of immunohistochemical staining showed that there was no significant difference in the number of proliferating(Ki67)cells in DG of hippocampus between NIHL and control groups.The spatial learning significantly promoted the survival of newborn cells in the control groups,however,this rescue effect was not seen in the NIHL groups.